This project is an attempt to understand the mechanism by which group A streptococcus modulates host defenses. These streptococci have evolved proteins including the C5a peptidase that destroys C5a, an important early signal that attracts protective phagocytes to infected tissue. The recent discovery that the peptidase is also a fibronectin and cell-binding protein has become a significant new focus. Experiments are planned to evaluate the importance of these activities, relative to peptidase activity in virulence using intranasal and subdermal mouse models of infection. Recognition that penicillin often fails to eliminate group A streptococci from throats of ill children and the recent resurgence of serious complications associated with streptococcal infections, has prompted an intense effort to develop preventive vaccines by industry and NIH. The C5a peptidase is a major focus of vaccine development, increasing the need to learn more about its role in virulence, and its impact on host defenses. New data indicates that the C5a peptide required for successful colonization and persistence of streptococci in nasal associated lymphoid tissue.